Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7YB7WD)

• DOT Name: E3 ubiquitin-protein ligase RNF181 (RNF181)
• Synonyms: EC 2.3.2.27; RING finger protein 181
• Gene Name: RNF181
• Related Disease:
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: RN181_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF13639
• Sequence:
  MASYFDEHDCEPSDPEQETRTNMLLELARSLFNRMDFEDLGLVVDWDHHLPPPAAKTVVE
  NLPRTVIRGSQAELKCPVCLLEFEEEETAIEMPCHHLFHSSCILPWLSKTNSCPLCRYEL
  PTDDDTYEEHRRDKARKQQQQHRLENLHGAMYT
• Function: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Catalyzes monoubiquitination of 26S proteasome subunit PSMC2/RPT1.
• Tissue Specificity: Widely expressed, with highest levels in liver and heart and lowest levels in brain and skeletal muscle. Expressed in platelets (at protein level).
• Reactome Pathway: E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of E3 ubiquitin-protein ligase RNF181 (RNF181).	[9]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of E3 ubiquitin-protein ligase RNF181 (RNF181).	[7]

References

• [1] Screening and verification of proteins that interact with HSPC238.Oncol Rep. 2015 Dec;34(6):3097-103. doi: 10.3892/or.2015.4289. Epub 2015 Sep 18.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.